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Small fiber neuropathy in unexpected clinical settings: a review.
No full textSmall fiber neuropathy (SFN) is being recognized with increasing frequency in neuromuscular practice due to improved diagnostic techniques. Although there are some common etiologies, up to one-third of cases are considered idiopathic. In recent years, several disorders have unexpectedly been reported in association with SFN, on clinical grounds and complementary investigations, including quantitative sensory testing, intraepidermal nerve fiber density and confocal corneal microscopy. Knowledge of these disorders is important in clinical practice as increased awareness enables prompt diagnosis of SFN in these settings and early optimal therapeutic management of affected patients. Furthermore, these new developments may lead to a better understanding of the pathophysiologic mechanisms underlying SFN in these different disorders as well as, in some cases, an expanded spectrum of affected organs and systems. This article reviews these reported associations, their possible pathophysiologic bases, and the potential resulting management implications. This article is protected by copyright. All rights reserved
European Headache Federation recommendations for neurologists managing giant cell arteritis.
No full textBACKGROUND AND AIM
Giant cell arteritis (GCA) remains a medical emergency because of the risk of sudden irreversible sight loss and rarely stroke along with other complications. Because headache is one of the cardinal symptoms of cranial GCA, neurologists need to be up to date with the advances in investigation and management of this condition. The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based recommendations on GCA.
METHODS
The working group identified relevant questions, performed systematic literature review and assessed the quality of available evidence, and wrote recommendations. Where there was not a high level of evidence, the multidisciplinary (neurology, ophthalmology and rheumatology) group recommended best practice based on their clinical experience.
RESULTS
Across Europe, fast track pathways and the utility of advanced imaging techniques are helping to reduce diagnostic delay and uncertainty, with improved clinical outcomes for patients. GCA is treated with high dose glucocorticoids (GC) as a first line agent however long-term GC toxicity is one of the key concerns for clinicians and patients. The first phase 2 and phase 3 randomised controlled trials of Tocilizumab, an IL-6 receptor antagonist, have been published. It is now been approved as the first ever licensed drug to be used in GCA.
CONCLUSION
The present article will outline recent advances made in the diagnosis and management of GCA
Pituitary metastases: presentation and outcomes from a pituitary center over the last decade.
No full textPURPOSE
Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center-over 10 years.
METHODS
Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed.
RESULTS
18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2-47).
CONCLUSIONS
In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors
'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab.
No full textBACKGROUND
The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension.
METHODS
Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0-1 or MG-QOL15 total score of 0-3.
RESULTS
At REGAIN week 26, more eculizumab-treated patients achieved 'minimal symptom expression' versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved 'minimal symptom expression' increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved 'minimal symptom expression' (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports.
CONCLUSIONS
Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained 'minimal symptom expression' based on patient-reported outcomes. 'Minimal symptom expression' may be a useful tool in measuring therapy effectiveness in gMG.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01997229, NCT02301624
Survival after out-of-hospital cardiac arrest in Europe - results of the EuReCa TWO study.
No full textBACKGROUND
The epidemiology and outcome after out-of-hospital cardiac arrest (OHCA) varies across Europe. Following on from EuReCa ONE, the aim of this study was to further explore the incidence of and outcomes from OHCA in Europe and to improve understanding of the role of the bystander.
METHODS
This prospective, multicentre study involved the collection of registry-based data over a three-month period (1 October 2017 to 31 December 2017). The core study dataset complied with the Utstein-style. Primary outcomes were return of spontaneous circulation (ROSC) and survival to hospital admission. Secondary outcome was survival to hospital discharge.
RESULTS
All 28 countries provided data, covering a total population of 178,879,118. A total of 37,054 OHCA were confirmed, with CPR being started in 25,171 cases. The bystander cardiopulmonary resuscitation (CPR) rate ranged from 13% to 82% between countries (average: 58%). In one third of cases (33%) ROSC was achieved and 8% of patients were discharged from hospital alive. Survival to hospital discharge was higher in patients when a bystander performed CPR with ventilations, compared to compression-only CPR (14% vs. 8% respectively).
CONCLUSION
In addition to increasing our understanding of the role of bystander CPR within Europe, EuReCa TWO has confirmed large variation in OHCA incidence, characteristics and outcome, and highlighted the extent to which OHCA is a public health burden across Europe. Unexplained variation remains and the EuReCa network has a continuing role to play in improving the quality management of resuscitation
How to WEB: a practical review of methodology for the use of the Woven EndoBridge.
No full textWide-necked bifurcation aneurysms (WNBAs) make up 26-36% of all brain aneurysms. Treatments for WNBAs pose unique challenges due to the need to preserve major bifurcation vessels while achieving a durable occlusion of the aneurysm. Intrasaccular flow disruption is an innovative technique for the treatment of WNBAs. The Woven EndoBridge (WEB) device is the only United States Food and Drug Administration approved intrasaccular flow disruption device. In this review article we discuss various aspects of treating WNBAs with the WEB device, including indications for use, aneurysm/device selection strategies, antiplatelet therapy requirement, procedural technique, potential complications and bailouts, and management strategies for residual/recurrent aneurysms after initial WEB treatment
Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.
No full textGraft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation
Maresin Conjugates in Tissue Regeneration 1 improves alveolar fluid clearance by up-regulating alveolar ENaC, Na, K-ATPase in lipopolysaccharide-induced acute lung injury.
No full textMaresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 ± 2.07 vs 10.11 ± 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na -K -adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS)
Risk Prediction Models for Out-of-Hospital Cardiac Arrest Outcomes in England.
No full textINTRODUCTION
The Out-of-Hospital Cardiac Arrest (OHCA) Outcomes project is a national research registry. One of its aims is to explore sources of variation in OHCA survival outcomes. This study reports the development and validation of risk prediction models for return of spontaneous circulation (ROSC) at hospital handover and survival to hospital discharge.
METHODS AND RESULTS
The study included OHCA patients who were treated during 2014 and 2015 by emergency medical services (EMS) from 7 English National Health Service ambulance services. The 2014 data were used to identify important variables and to develop the risk prediction models, which were validated using the 2015 data. Model prediction was measured by area under the curve (AUC), Hosmer-Lemeshow test, Cox calibration regression and Brier score. All analyses were conducted using mixed effects logistic regression models. Important factors included age, gender, witness/bystander cardiopulmonary resuscitation (CPR) combined, aetiology and initial rhythm. Interaction effects between witness/bystander CPR with gender, aetiology and initial rhythm and between aetiology and initial rhythm were significant in both models. The survival model achieved better discrimination and overall accuracy compared with the ROSC model (AUC=0.86 vs 0.67, Brier score=0.072 vs 0.194, respectively). Calibration tests showed over- and under-estimation for the ROSC and survival models, respectively. A sensitivity analysis individually assessing Index of Multiple Deprivation scores and location in the final models substantially improved overall accuracy with inconsistent impact on discrimination.
CONCLUSION
Our risk prediction models identified and quantified important pre-EMS intervention factors determining survival outcomes in England. The survival model had excellent discrimination